Man up: Is testosterone an elixir of youth?

“There’s also a problem that the ‘normal’ ranges for one
laboratory may be decidedly different than they are for another
laboratory,” says Ronald Swerdloff, chief endocrinologist at Harbor
UCLA Medical Center in California and LA Biomed Inv.
Testosterone supplements promise men a butch boost of resurrected
libido, energy and mood. But there’s a better way to restore
virility

“REDUCED sex drive? Decreased energy? Unwanted mood or body changes?
Is it low testosterone?”

TV adverts asking these questions have been bombarding American men
for the past five years, often accompanied by images of handsome
ageing men shooting basketball hoops or sharing romantic moments
with attractive women.

The remedy, they suggest, is testosterone supplements; often billed
as a quick ticket back to youth, fitness and virility. Elsewhere,
the marketing is less pervasive, but worries about the physical
deterioration that accompanies male ageing are similar.

But what if we’ve got testosterone all wrong? Testosterone is widely
perceived as the masculinity hormone; associated with virility,
strength and competition, so it’s understandable that men might
reach for it to restore a flagging mojo. However, testosterone may
not be the express ticket back to youth many perceive it to be.
Boosting levels may even be harmful. Neither does testosterone only
facilitate stereotypically male behaviours like aggression and
competitiveness; it may have a gentle side. “Pop culture has
promoted the idea that if enough [testosterone] is good, more is
even better,” says Bradley Anawalt at the University of Washington
Medical Center in Seattle. “But it doesn’t make you a better man.”

Between 2000 and 2011, prescriptions for testosterone supplements in
the US more than quadrupled [16](see graph) and in 2011 an estimated
[17]5.3 million prescriptions were issued. Although nowhere near US
figures yet, sales of testosterone supplements in the UK, Australia
and Germany are also on the increase.

Hany Omar, a 42-year-old mortgage broker in Washington DC, is among
the growing ranks of testosterone aficionados. He had his hormone
levels tested after he started to feel overly tired after regular
gym workouts. At 380 nanograms per decilitre (ng/dl), his
testosterone level was well within the normal range. There also
seemed to be nothing wrong with his overall health, so he found a
urologist willing to prescribe testosterone to anyone who tested
below 400 ng/dl. Since last summer he has been injecting himself
with testosterone every two weeks. “My libido is stronger, I have
more energy, I have great workouts,” Omar says. “I don’t want to
call it the fountain of youth, but that’s what it feels like.”

Man enough?

Testosterone is a product that caught the public’s fancy long before
anyone could fully explain its merits, perils, or whether the
balance between them justified its growing presence in men’s
medicine cabinets. First synthesised in the 1930s, it was used for
decades to treat conditions in which men are either born with
extremely low testosterone, or lose their ability to produce it
because of serious illness or injury. Testosterone drives the
development of the testes, prostate gland and secondary sexual
characteristics like body hair; in adult men it regulates sex drive,
bone mass, muscle strength, and the production of sperm and red
blood cells. “You need to have normal amounts of testosterone to
feel good and maintain muscle mass and so forth,” Anawalt says.

Of course, testosterone can also influence behaviour. Male
swaggering and boasting are often dismissed as a displays of
testosterone, as is aggression and risk-taking. This reputation
possibly stems from a series of studies starting in the 1970s, which
correlated extremely high testosterone with aggressive behaviour in
criminals. More recently, high testosterone has been linked to stock
market success among [18]city traders.

However, recent research is painting a far more nuanced portrait of
this hormone; suggesting that it prompts us to act in ways that
might boost our social status – be that through aggression, or
other, gentler means. “This hormone is smart,” says Jack van Honk of
Utrecht University in the Netherlands. “It finds other ways to reach
dominance, without reverting to cheating or aggression.”

Some of the evidence comes from a surprising source: women. All
adult women produce testosterone, but in far smaller quantities than
men, making it easier to assess how a temporary testosterone boost
affects behaviour. “Even though hormonal systems are not exactly the
same in men and women, there are a lot of similarities in the way
basic social behaviours are influenced by hormones, especially
testosterone,” van Honk says.

In one study, he and his colleagues asked women to view photos of
strangers and rate them according to how trustworthy they looked.
Women who received testosterone supplements were [19]less likely to
rate people as trustworthy, but only if they were naturally very
trusting – suggesting it might boost wariness among those who are at
high risk of being misled by others, van Honk says.

In other situations, testosterone appears to boost generosity. In
one study, women were given EUR20, and asked if they’d like to
invest some of it in another player, the “trustee”. Any invested
money would be trebled, but it would be down to the trustee to
decide whether to give any money back. Investors given a dose of
testosterone tended to make stingier investments, but trustees who
were given [20]extra testosterone were more generous with their
payback – as if repaying the trust that had been placed in them.
This supports the idea that testosterone adjusts behaviour to the
situation at hand, says Maarten Boksem at Erasmus University in the
Netherlands, who led the study. “Being pro-social and actually
taking care of the people we need is very important for maintaining
high social status.”

The conventional wisdom is that levels of testosterone peak at
around the age of 20 and then slowly and steadily decline. Young men
are often perceived to be less risk-averse and more aggressive.
Combined with testosterone’s known role in physical development,
this gave rise to the understandable conclusion that the reduced
virility and vitality that occurs with age must be linked to
testosterone deficiency. And when easy-to-apply topical testosterone
treatments such as skin patches and gels began hitting the market in
the early 2000s, testosterone took on a whole new persona as a
cure-all for anything that might ail the ageing male, from erectile
dysfunction to unwanted body fat. This despite a growing body of
evidence suggesting that many of the major attributes assigned to
testosterone might, in fact, be myths (see “[21]Testosterone
Truths”).

Inevitable decline

Yet it is far from clear what constitutes a normal decline of
testosterone as men age. One problem is that there is widespread
disagreement about what level of testosterone counts as abnormally
low. Surprisingly, there isn’t even a standard method of assessing
it, meaning that sending the same blood sample to different labs can
give different results. Testosterone levels can vary widely
depending on several factors, including the time of day and activity
levels. “There’s also a problem that the ‘normal’ ranges for one
laboratory may be decidedly different than they are for another
laboratory,” says Ronald Swerdloff, chief endocrinologist at Harbor
UCLA Medical Center in California. Having recognised this, the US
Centers for Disease Control are now trying to standardise
testosterone testing.

Further clues about what testosterone is doing to our brains and
bodies come from another unlikely source – a remote Amazon tribe
called the Tsimane.

Curiously, baseline levels of the hormone are a third lower on
average among Tsimane men than in their American counterparts.
They’re certainly no less manly, at least in the conventional sense;
they survive by hunting, fishing and farming. But recent research
suggests that it’s not necessarily how much testosterone you start
with, but how your body responds to it that counts. It also hints
that a person’s baseline testosterone level – the focus of most
clinical tests – may be a poor marker of what’s going on in their
bodies.

In one study, Tsimane men provided saliva samples before and
immediately after competing in a soccer match, which were tested for
testosterone. Playing soccer caused testosterone levels to rise by
about 30 per cent, just as they do in American men in similar
scenarios. Further studies indicate that it also shoots up when
Tsimane men are hunting or clearing horticultural plots – activities
that raise their social status in the community, says Benjamin
Trumble, an anthropologist at the University of Washington, Seattle,
who led the research. The reason for these spikes is probably
physical as well as behavioural; one of testosterone’s most
important jobs is to supply energy to muscles.

The implication is that your ability to mobilise the hormone at
times of need is potentially more important than how much
testosterone you start with. “Men who can still chop trees in their
80s have the same relative increases in testosterone as men in their
20s and 30s,” says Trumble, who has tested Tsimane men of various
ages.

The idea of an inevitable plummet in testosterone with age is also
called into question by studies of Tsimane men, whose levels seem to
remain relatively constant throughout adult life. A recent study of
1500 Australian men suggested that they too might maintain
reasonable levels of testosterone into old age – provided they
maintain a healthy lifestyle. The five-year study showed an average
0.8 per cent decline in testosterone each year – but men who
[22]were obese, depressed or who smoked accounted for most of the
decline. Removing them made the decline too small to be clinically
significant.

Yet other studies also hint that avoiding weight gain and staying
active could be crucial for enabling testosterone to do its job.
When testosterone comes into contact with fat tissue, it changes
into a form of oestrogen, thanks to an enzyme in fat cells called
aromatase. Yet the area of the brain that regulates testosterone
production doesn’t detect this change because the hormones have such
similar structures. As a result, normal testosterone signalling in
the body becomes confused. To make matters worse, oestrogen promotes
the laying down of even more body fat, which causes further
confusion.

It could be tempting, then, to think that taking a supplement would
be a good idea for ageing men – particularly those developing a
middle-age spread. Even if men can get by with lower levels of
testosterone like the Tsimane do, surely very low levels of it are
unhealthy? However, testosterone supplements might potentially do
more harm than good. A recent study by Bu Yeap at the University of
Western Australia and colleagues found that both high and low
testosterone levels were associated with a shorter lifespan than
middling levels of the hormone.

And in January, the US Food and Drug Administration announced that
it was reviewing the safety of marketed versions of the hormone in
the wake of [23]two studies suggesting an [24]increased risk of
heart attacks, stroke and death among men taking it. The European
Medicines Agency announced a similar review in April.

Since testosterone can boost red blood cell numbers, one possible
explanation is that it causes the blood to thicken, which might
increase the risk of clots – effects the makers of gels and other
topical products already state on their labels. However, much
remains unknown, and the studies suggesting harmful effects were
observational, not the double-blind, placebo-controlled studies
generally relied upon to assess a drug’s risk.

Besides heart attacks, other studies have hinted that high
testosterone levels might raise the risk of prostate cancer. Since
cancer and heart problems are diseases connected with age, one
suggestion is that the natural decline of hormones may be protecting
us from diseases of ageing. “If humans evolved certain systems to
prevent or postpone disease, then the gradual reduction in
testosterone level [with age] is something the body is doing to
prevent damage,” says John Hoberman, author of Testosterone Dreams.
Proving this idea is difficult, however, because establishing the
precise causes of age-related diseases is tricky.

How do you keep your testosterone levels on an even keel rather than
see them drop off a cliff? Artificially boosting testosterone may
seem like a quick fix but we are still a long way from knowing
whether such a strategy is either smart or safe. “The medical
community and patients are abusing testosterone therapy in ways that
are completely outside of the evidence,” says Daniel Shoskes, a
urologist at the Cleveland Clinic in Ohio. “A drug with such
potential for both benefit and harm shouldn’t just be thrown around
like this.”

Why not adopt a healthy lifestyle – a study of 900 men found that
obese men who lost an average of 8 kilograms through diet and
exercise over a year had a corresponding increase in testosterone
levels.

Given how patchy our understanding of testosterone is, a sensible
first step for older men with a flagging mojo might be to reach for
the running shoes, rather than testosterone supplements.

Testosterone truths

Claim: Testosterone will boost your sex drive and correct erectile
dysfunction

Fact: Studies have found that testosterone supplements produce only
a moderate increase in libido and have virtually no effect on
erectile dysfunction or overall sexual satisfaction in men. The
theory that testosterone might improve female libido is also far
from proven. A testosterone patch developed for women was rejected
by the US Food and Drug Administration in 2004 because it had little
impact on sexual desire, and carried potential cardiovascular risks
Claim: If you feel tired, your testosterone may be running low

Fact: None of the trials of marketed testosterone supplements were
designed to measure fatigue. A one-year study currently being run by
the National Institutes of Health is assessing the hormone’s impact
on vitality and anaemia, but data won’t be out until late 2014
Claim: Testosterone supplements will make you stronger and leaner

Fact: Studies of testosterone supplementation have shown that
although it produces a slight increase in lean body mass, and
decreases fat mass by up to 2 kilograms, testosterone causes no
change in overall body weight when compared with placebo
Claim: Testosterone improves sporting prowess

Fact: Some trials have shown small increases in muscle mass and
slight improvements in grip strength with testosterone
supplementation. The hormone also raises red blood cell counts,
which may boost the amount of oxygen carried in the blood. However,
studies measuring the hormone’s effects on lower limb strength and
overall physical function have produced inconsistent results
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